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Biomedical subjects

K Yanai

Publications and source records attributed to K Yanai.

At least 91 records · Page 5Linked to original sources
PubMed1995

[In vivo visualization of neurotransmitter function in the human brain by PET].

Measurement of cerebral blood flow and energy metabolism using PET with 15O and 18F labeled tracers allows quantitative evaluation of cerebral metabolism that can be perturbed in pathological states. Neurotransmission is a new target that is visualized by labeling of substrates of enzymes that are involved in neurotransmitter synthesis or degradation. Neuronal receptors are mapped by introducing the labeled ligands that are specifically bound to the receptors in question. We developed unique tracers that label dopamine D2 or histamine H1 receptors. With other available ligands for the muscarinic cholinergic receptors and [18F] fluorodopa, we started clinical investigations to document the state of neurotransmission in patients with epilepsy, Parkinson's disease and dementia. Using [11C] doxepin we observed an increase of H1 receptors in the epileptic foci that showed decreased glucose metabolic rate at the interictal phase. This phenomenon is compatible with reported increase of mu opiate receptors in the brains of epileptic patients. Brain uptake of FDOPA (Ki), calculated by the graphical plot was found relatively stable with age both in the normal population and dementia patients. However, the striatal Ki of FDOPA of severely demented patients significantly reduced, compared with the normal aged subjects. The correlation analysis between FDOPA Ki and severity of dementia as assessed by mini-mental state examination revealed a significant reduction of Ki associated with the disease progression. Increase in D2 receptor density as assessed by the uptake of YM 09151-2 was observed in cases with reduced FDOPA uptake, which may correspond to the state of supersensitivity of the D2 receptors.

Brain↗
PubMed1995

Positron emission tomographic study of central histamine H1-receptor occupancy in human subjects treated with epinastine, a second-generation antihistamine.

Histamine H1-receptor occupancy in the human brain was measured in healthy young volunteers by positron emission tomography (PET) using [11C]doxepin. d-Chlorpheniramine, a selective and classical antihistamine, occupied 76.8 +/- 4.2% of the averaged values of available histamine H1 receptors in the frontal cortex after its administration in a single oral dose of 2 mg. Epinastine, a non-sedative antihistamine, occupied 13.2 +/- 18.5% of the available H1 receptors in the human frontal cortex after its administration in a single oral dose of 20 mg. There was significant correlation between H1 receptor occupancy by epinastine and its plasma concentration in each subject. PET data on the human brain were essentially compatible with those on H1-receptor occupancy in the guinea pig brain as determined by an in vivo binding technique, although for the same H1-receptor occupancy, the dose was less in humans than in guinea pigs. Our PET studies demonstrated that receptor occupancy by a second-generation H1 antagonist, epinastine, was less than 20% of the total H1 receptors, and that the low receptor occupancy was closely related to the low incidence of central side effects.

Adult↗
PubMed1994

Histamine depletion in brain caused by treatment with (S)alpha-fluoromethylhistidine enhances ischemic damage of gerbil hippocampal CA2 neurons.

The effect of (S)alpha-fluoromethylhistidine (FMH), a specific inhibitor of histamine synthesis from histidine, on ischemic damage was examined in gerbil brain after forebrain ischemia. Two h after subcutaneous FMH injection, the histamine content of the brain was significantly reduced. Neuronal loss in the CA2 region of the hippocampus 7 days after 3 min ischemia was enhanced by treatment with FMH. These results indicate that depletion of brain histamine aggravates neuronal death of hippocampal CA2 neurons after 3 min ischemia.

Animals↗
PubMed1994

Marked increase in histamine H3 receptors in the striatum and substantia nigra after 6-hydroxydopamine-induced denervation of dopaminergic neurons: an autoradiographic study.

The bindings of [3H](R) alpha-methylhistamine to histamine H3 receptors were investigated in rat brain following intranigral treatment with 6-hydroxydopamine (6-OHDA) by quantitative receptor autoradiography. The levels of [3H](R) alpha-methylhistamine binding sites in the denervated striatum (dorsomedial and dorsolateral) and substantia nigra were significantly higher than those in the contralateral side 21 days after nigral lesions. Saturation kinetic analysis revealed that the maximum binding capacities were up-regulated to about 1.7- and 1.2-fold those in the contralateral substantia nigra and striatum, respectively. These results strongly suggest that H3 receptors in the striatum and substantia nigra are influenced by tonic dopaminergic inputs.

Animals↗
PubMed1994

Marked increase in [3H](R) alpha-methylhistamine binding in the superior colliculus of visually deprived rats after unilateral enucleation.

The binding of [3H](R)alpha-methylhistamine to histamine H3-receptors in visual structures of unilaterally enucleated rats was examined by quantitative autoradiography to clarify the involvement of histamine neurons in the visual system. [3H](R)alpha-Methylhistamine binding in the visually deprived superior colliculus, contralateral to the enucleated eye, was significantly increased 5, 15, 30 and 45 days after unilateral enucleation. Slight time-dependent increases in ligand binding were observed in the visual cortex, but the change was significant only 45 days after unilateral enucleation. Unilateral enucleation had no significant effect in the dorsal lateral geniculate nucleus at any time after enucleation. Continuous injection of (S)-alpha-fluoromethylhistidine, a specific inhibitor of L-histidine decarboxylase, attenuated the effect of unilateral enucleation in the superior colliculus. These results suggest that retinal deafferentation induced an increase in histamine H3-receptor binding sites, probably by selective adjustment of histamine neurons in response to unilateral enucleation.

Animals↗
PubMed1994

Heterogeneous distributions of histamine H3, dopamine D1 and D2 receptors in rat brain.

The changes of the histamine H3 and dopamine D1 or D2 receptor binding sites induced by quinolinic acid treatment were studied in order to discriminate the comparative distribution. This treatment resulted in similar decreases in histamine H3 and dopamine D1 receptor binding sites in the striatum and ipsilateral substantia nigra. Dopamine D2 receptor binding sites were relatively well conserved, whereas H3 receptors decreased considerably. These results suggest that histamine H3 and dopamine D1 receptor binding sites are localized on the striatonigral projection neurones which are together sensitive to quinolinic acid, and that the distributional compartment of dopamine D2 receptor binding sites is quite different from those of histamine H3 and dopamine D1 receptors.

Animals↗
PubMed1994

Cloning and characterization of two 3-phosphoglycerate kinase genes of Rhizopus niveus and heterologous gene expression using their promoters.

Two 3-phosphoglycerate kinase genes (pgk1 and pgk2) were cloned from Rhizopus niveus. It was deduced that both pgk genes have two introns. They have open reading frames of 1,355 bp and 1,356 bp, and code for proteins of 417 and 416 amino acids, respectively. The first introns of both genes are located at similar positions as those of pgk genes from other fungi based on the deduced amino-acid sequences of PGK proteins. The position of their second introns was similar to that of the seventh intron of the human pgk gene. The deduced amino-acid sequences of PGK proteins show high identity (64.8-72.2%) to those of PGKs of other filamentous fungi. When the promoters of each of the pgk genes were fused to the E. coli beta-glucuronidase (GUS) gene and introduced into R. niveus, significant GUS activities were detected in the cell lysates of the transformants, suggesting that GUS protein was expressed under the control of both pgk gene promoters in R. niveus. GUS activity was induced by glucose but not by glycerol, indicating that expression of R. niveus pgk genes was regulated by the carbon source.

Bacterial Proteins↗
PubMed1994

[Visualization of neurotransmitter receptors in the living human brain by position emission tomography (PET)].

Various brain imaging techniques have become available in the past decade. These include techniques to evaluate brain structure using X-ray computerized tomography or magnetic resonance imaging and techniques to assess brain functional activities (cerebral blood flow, brain energy metabolism and brain protein synthesis) using positron emission tomography (PET). PET also makes it possible for the first time to evaluate the states of various types of neurotransmitter receptors, such as dopamine D2 and D1, serotonin 5-HT2, muscarinic cholinergic, opiate, benzodiazepine and histamine H1, and to determine the state of monoamine oxidase (A and B) under in vivo conditions. These techniques cannot only be used to map "brain neurochemistry" in normal human beings, but they will also increase our knowledge by demonstrating neurochemical abnormalities in a wide range of neurological and psychiatric disorders or those that happen during normal aging. The PET techniques may be applicable to the development of new drugs in the pharmaceutical industry. We have been exploring the methodology of using 11C-labeled antagonists for mapping functional neurotransmitter receptors in human brain directly and noninvasively by PET. The present review article provides an outline of the conceptual and methodological progress over the past several years that has made it possible to visualize neurotransmitter receptors in the living human brain by PET on the basis of our original work.

Adult↗
PubMed1994

Binding characteristics of a histamine H3-receptor antagonist, [3H]S-methylthioperamide: comparison with [3H](R)alpha-methylhistamine binding to rat tissues.

The release and synthesis of neuronal histamine are regulated by histaminergic autoreceptors named as histamine H3 receptors. The development of radiolabeled histamine H3 antagonists is needed to characterize the binding of antagonists to these receptors. Here we describe the binding characteristics of a new histamine H3-receptor antagonist, [3H]S-methylthioperamide (SMT), to rat tissues, and compare its binding with that of [3H](R)alpha-methylhistamine ((R)alpha MH), a selective histamine H3-receptor agonist. The binding of [3H]SMT to the membranes of rat forebrain was found to be stereoselective, saturable, reversible and temperature-dependent. Saturation binding experiments indicated a single class of high affinity sites for [3H]SMT in forebrain membranes (KD = 2.1 nM, Bmax = 24.3 pmol/g of tissue at 4 degrees C). The Bmax was approximately 3 times that of [3H](R)alpha MH binding to rat forebrain membranes (KD = 2.5 nM, Bmax = 7.3 pmol/g of tissue at 25 degrees C). Autoradiographic images of [3H]SMT binding in the brain were essentially the same as those of [3H](R)alpha MH. [3H]SMT also bound appreciably to peripheral tissues (the liver, adrenal, stomach, ileum, kidney, lung and bladder), whereas the [3H](R)alpha MH bindings to these peripheral tissues were negligible. These results indicate that [3H]SMT binds to H3 receptors primarily in the central nervous system, and that it also has high affinity toward non-H3 receptors, probably hemoproteins, in peripheral tissues.

Animals↗
PubMed1994

Isolation and characterization of two chitin synthase genes from Aspergillus nidulans.

Two chitin synthase genes, designated chsA and chsB, were isolated from Aspergillus nidulans with the Saccharomyces cerevisiae CHS2 gene as the hybridization probe. Nucleotide sequencing showed that chsA and chsB encoded polypeptides consisting of 1013 and 916 amino acid residues, respectively; the hydropathy profiles of the enzymes were similar to those of other fungal chitin synthases. Northern analysis indicated that both genes were transcribed, suggesting that cellular chitin in A. nidulans is synthesized by at least two chitin synthases. For examination of the roles of the chitin synthase genes in cell growth, gene disruption experiments were done. The chsA disruptant grew as well as the wild-type strain, but the chsB disruptant had severe growth defects that could not be overcome by the addition of 1.2M sorbitol as an osmotic stabilizer. These findings suggested that chsB but not chsA is essential for hyphal growth.

Amino Acid Sequence↗
PubMed1994

[Manic-depressive states induced by drugs and various diseases].

Manic-depressive states caused by drugs and various diseases consist of symptomatic psychosis, organic psychosis and toxic psychosis. Disturbance of consciousness is common to symptomatic psychosis. Emotional disturbance is associated with it. Dementia, personality change and disturbance of consciousness are common to organic psychosis. Emotional disturbance is also associated with these. Drug-induced manic-depressive states are classified by some studies. Drug-induced manic-depressive states are often caused by drugs for physical diseases. They are not originally psychotropic drugs. And they have affinity to the central nerve system, to some degree. Interferons cause disturbance of consciousness or delirious state in the acute phase and depressive state or numerous psychiatric symptoms in the chronic phase.

Female↗
PubMed1993

Effects of (S)-alpha-fluoromethylhistidine and (R)-alpha-methylhistamine on locomotion of W/Wv mice.

We studied the effects of inactivators of the central histaminergic neuron system, (R)-alpha-methylhistamine, a histamine H3 receptor agonist, and (S)-alpha-fluoromethylhistidine, a histamine synthesis inhibitor, on locomotor activity and brain histamine content of mast cell-deficient W/Wv mice using a recently developed high-performance liquid chromatography system coupled with a fluorometric detector. IP injection of (R)-alpha-methylhistamine (6-50 mg/kg) increased brain histamine content after 1 h but caused no significant change in locomotor activity. IP injection of (S)-alpha-fluoromethylhistidine decreased brain histamine content at doses of 6-50 mg/kg and locomotor activity at doses of 12.5-50 mg/kg. However, locomotor activity was decreased significantly (in Student's t-test) by sequential administrations of (S)-alpha-fluoromethylhistidine (6 mg/kg) and (R)-alpha-methylhistamine (12.5 or 25 mg/kg), but not by (S)-alpha-fluoromethylhistidine (6 mg/kg) and other doses of (R)-alpha-methylhistamine (6 or 50 mg/kg). These results support the hypothesis that the central histaminergic neuron system is involved in the control of spontaneous locomotion or alertness.

Animals↗
PubMed1993

Proconvulsant effect of ketotifen, a histamine H1 antagonist, confirmed by the use of d-chlorpheniramine with monitoring electroencephalography.

Ketotifen produced seizures in a 5-year-old boy with secondary generalized epilepsy (SGE) and allergic rhinitis. To confirm that the seizures were due to histamine H1 receptors blockade, d-chlorpheniramine was administered with monitoring electroencephalography (EEG). Administration of d-chlorpheniramine significantly increased the number of epileptic discharges in the patient, compared with those before administration. Plasma noradrenaline and dopamine levels were not affected by treatment with d-chlorpheniramine. These findings indicate that histamine H1 receptors blockade produced convulsions and increased epileptic discharges on EEG. Recently, several experimental reports have shown that histamine has an inhibitory role on convulsions through histamine H1 receptors. Experimental findings and present results show that histamine H1 antagonists have proconvulsant effects, especially in the developmental period. Thus, it is recommended that centrally-acting histamine H1 antagonists should be avoided in epileptic patients, especially in children of pre-school age.

Child, Preschool↗
PubMed1992

Effects of the histamine H3 receptor ligands thioperamide and (R)-alpha-methylhistamine on histidine decarboxylase activity of mouse brain.

The effects of the histamine H3 receptor ligands thioperamide and (R)-alpha-methylhistamine on the histidine decarboxylase (HDC) activity and histamine content of mouse brain were examined. Thioperamide, a histamine H3 antagonist, significantly increased the HDC activity in the brain of ddY, W/Wv and ICR mice 2-6 hr after its intraperitoneal (i.p.) injection. On the other hand, (R)-alpha-methylhistamine, a histamine H3-receptor agonist, caused no significant change in the HDC activity. The whole brain histamine content of ddY mice decreased significantly to 60-70% of the control level 2-8 hr after injection of thioperamide (25 mg/kg, i.p.), but then increased to 90% of the control level 10 hr after the injection. These in vivo results showed that blockade of the presynaptic histamine H3-receptor, which causes release of presynaptic histamine, increased the HDC activity.

Animals↗
PubMed1992

Histamine H1 receptors in human brain visualized in vivo by [11C]doxepin and positron emission tomography.

Histamine H1 receptors in the living human brain were visualized by positron emission tomography (PET) using [N-11C-methyl]-(E)-doxepin ([11C]doxepin). The regional distribution of the carbon-11-labeled compound in the brain corresponded well with that of the histamine H1 receptors measured in vitro using [3H]pyrilamine. The radioactivity in the brain was significantly reduced by intravenous pretreatment with d-chlorpheniramine (5 mg), a histamine H1 antagonist. The regional distribution of [11C]doxepin in the brain 45-90 min after its injection was almost the same as that of [11C]pyrilamine in the brain. These results indicate that [11C]doxepin is useful for measuring histamine H1 receptors in human brain by PET.

Adult↗
PubMed1992

Histamine levels and clonic convulsions of electrically-induced seizure in mice: the effects of alpha-fluoromethylhistidine and metoprine.

The purpose of this study was to investigate the possible role of the central histaminergic neuron system in electrically-induced seizure in mice. For this purpose, we examined the effects of intraperitoneal (i.p.) injections of histaminergic agents, such as L-histidine, metoprine, and alpha-fluoromethylhistidine (FMH), on electrically-induced seizure. L-Histidine decreased the duration of clonic convulsion in electrically-induced seizure, but not affected that of tonic convulsion. This effect of L-histidine was antagonized by pretreatment with FMH, indicating that it was due to histamine formed by decarboxylation of L-histidine in the central nervous system. The anticonvulsive effect of L-histidine was also reduced by the H1-antagonist pyrilamine, but not by the H2-antagonist zolantidine, indicating that the effect on electrically-induced seizure is mediated through central H1-receptors. Metoprine, which increased the histamine levels in the cerebral cortex, diencephalon and midbrain of mice, decreased the duration of clonic convulsions dose-dependently. Conversely, FMH, which decreased the brain histamine levels, increased the duration of clonic convulsions. Good inverse correlations were found between the duration of clonic convulsions and brain histamine levels, especially in the diencephalon: the histamine levels were inversely proportional to the duration of clonic convulsions. No correlation was found between the duration of tonic convulsions and brain histamine levels. These results suggest that the histaminergic neuron system is important in inhibition of the duration of clonic convulsion on electrically induced seizure in mice.

Animals↗
PubMed1992

Calcium mobilization and its desensitization induced by endothelins and sarafotoxin in human astrocytoma cells (1321N1): comparison of histamine-induced calcium mobilization.

Intracellular free Ca2+ concentration ([Ca2+]i) was monitored in monolayer of 1321 N1 astrocytoma cells by using a fluorescent Ca2+ indicator fura-2. Endothelin-1 (ET-1), endothelin-2 (ET-2), and sarafotoxin Sb6 (SRTX) increased [Ca2+]i from 56 +/- 6 nM to 360 +/- 82, 120 +/- 51, 143 +/- 29 nM, respectively, immediately after their addition to the perfusate with maximum response of more than 0.1 microM of peptides. Endothelin-3 (less than 1 microM) did not affect [Ca2+]i. The increase in [Ca2+]i in response to either ET-1, ET-2, or SRTX could be almost completely inhibited by pretreating cells with ET-1 or ET-2. The homologous desensitization of [Ca2+]i induced by ETs and SRTX is in good agreement with their affinity toward an ETA receptors. The responses in [Ca2+]i by ETs and SRTX were not affected in the desensitized state induced by the pretreatment of histamine in the presence of extracellular Ca2+. However, the response in [Ca2+]i by ETs and SRTX were reduced in the desensitized state induced by pretreatment of histamine in the absence of extracellular Ca2+. These results indicate that depletion of the intracellular Ca2+ stores is responsible for the heterologous desensitization between ETs and histamine.

Calcium↗